BACKGROUND: Given the recent interest in light-emitting diode (LED) photomodulation and minimally invasive nonablative laser therapies, it is timely to investigate reports that low-level laser therapy (LLLT) may have utility in wound healing. OBJECTIVES: To critically evaluate reported in vitro models and in vivo animal and human studies and to assess the qualitative and quantitative sufficiency of evidence for the efficacy of LLLT in promoting wound healing. METHOD: Literature review, 1965 to 2003. RESULTS: In examining the effects of LLLT on cell cultures in vitro, some articles report an increase in cell proliferation and collagen production using specific and somewhat arbitrary laser settings with the helium neon (HeNe) and gallium arsenide lasers, but none of the available studies address the mechanism, whether photothermal, photochemical, or photomechanical, whereby LLLT may be exerting its effect. Some studies, especially those using HeNe lasers, report improvements in surgical wound healing in a rodent model; however, these results have not been duplicated in animals such as pigs, which have skin that more closely resembles that of humans. In humans, beneficial effects on superficial wound healing found in small case series have not been replicated in larger studies. CONCLUSION: To better understand the utility of LLLT in cutaneous wound healing, good clinical studies that correlate cellular effects and biologic processes are needed. Future studies should be well-controlled investigations with rational selection of lasers and treatment parameters. In the absence of such studies, the literature does not appear to support widespread use of LLLT in wound healing at this time. Although applications of high-energy (10-100 W) lasers are well established with significant supportive literature and widespread use, conflicting studies in the literature have limited low-level laser therapy (LLLT) use in the United States to investigational use only. Yet LLLT is used clinically in many other areas, including Canada, Europe, and Asia, for the treatment of various neurologic, chiropractic, dental, and dermatologic disorders. To understand this discrepancy, it is useful to review the studies on LLLT that have, to date, precluded Food and Drug Administration approval of many such technologies in the United States. The fundamental question is whether there is sufficient evidence to support the use of LLLT.

Erdle BJ, Brouxhon S, Kaplan M, Vanbuskirk J, Pentland AP.

Effects of continuous-wave (670-nm) red light on wound healing.

Dermatol Surg. 2008 Mar;34(3):320-5. Epub 2007 Dec 20.

BACKGROUND: Recent work suggests that injuries can heal faster if treated by lasers emitting 670-nm red light. LED lights emitting 670-nm light are now available. This suggests that inexpensive and easy-to-use 670-nm LED lights might help accelerate cutaneous wound healing. OBJECTIVE: The objective was to evaluate the effect of 670-nm LED light on wound healing in SKH-1 hairless mice. METHODS: To study 670-nm light effects on incisional injury, animals were left unexposed or exposed to equal doses of high-, medium-, or low-flux light. Burn injuries were treated with high-flux light or left unexposed. Healing was assessed by measurement of the burn area and the gap remaining to closure of incisional injury. RESULTS: Mice exposed to 670-nm red light showed significantly faster healing than control mice. High, medium, and low fluxes of light were all effective after incisional injury. In burn injury, there was improvement in wound healing initially, but the time to repair was unchanged. CONCLUSIONS: A 670-nm LED red light source accelerates healing in skin of SKH-1 hairless mice after incisional injuries, but is not as effective for burn injuries. These data that suggest red light exposure may be helpful in postoperative wound repair.

Lang-Bicudo L, Eduardo Fde P, Eduardo Cde P, Zezell DM.

LED phototherapy to prevent mucositis: a case report.

Photomed Laser Surg. 2008 Dec;26(6):609-13.

OBJECTIVE: The purpose of this case report was to evaluate the efficacy of phototherapy using light-emitting diodes (LEDs) to prevent oral mucositis in a Hodgkin\'s disease patient treated with the ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) chemotherapy regimen. BACKGROUND DATA: Mucositis is a common dose-limiting complication of cancer treatment, and if severe it can lead to alterations in treatment planning or suspension of cancer therapy, with serious consequences for tumor response and survival. Therefore, low-power lasers and more recently LEDs, have been used for oral mucositis prevention and management, with good results. MATERIALS AND METHODS: In this study, a 34-year-old man received intraoral irradiation with an infrared LED array (880 nm, 3.6 J/cm2, 74 mW) for five consecutive days, starting on chemotherapy day 1. In each chemotherapy cycle, he received the ABVD protocol on days 1 and 15, and received LED treatment for 5 d during each cycle. To analyze the results, the World Health Organization (WHO) scale was used to grade his mucositis, and a visual analogue scale (VAS) was used for pain evaluation, on days 1, 3, 7, 10, and 13 post-chemotherapy. RESULTS: The results showed that the patient did not develop oral mucositis during the five chemotherapy cycles, and he had no pain symptoms. CONCLUSION: LED therapy was a safe and effective method for preventing oral mucositis in this case report. However, further randomized studies with more patients are needed to prove the efficacy of this method.

PMID: 19025412

Caetano KS, Frade MA, Minatel DG, Santana LA, Enwemeka CS.

Phototherapy Improves Healing of Chronic Venous Ulcers.

Photomed Laser Surg. 2009 Jan 16.

Abstract Objective: We tested the hypothesis that LED phototherapy with combined 660-nm and 890-nm light will promote healing of venous ulcers that failed to respond to other forms of treatment. Background Data: A variety of dressings, growth factors, and adjunct therapies are used to treat venous ulcers, but none seems to yield satisfactory results. Materials and Methods: We used a randomized placebo-controlled double-blind study to compare a total of 20 patients divided with 32 chronic ulcers into three groups. In group 1 the ulcers were cleaned, dressed with 1% silver sulfadiazine (SDZ) cream, and treated with placebo phototherapy (<.03 J/cm(-3)) using a Dynatron Solaris 705((R)) phototherapy research device. In group 2 the ulcers were treated similarly but received real phototherapy (3 J/cm(-2)) instead of placebo. In group 3 (controls), the ulcers were simply cleaned and dressed with SDZ without phototherapy. The ulcers were evaluated with digital photography and computer image analysis over 90 d or until full healing was attained. Results: Ulcers treated with phototherapy healed significantly faster than controls when compared at day 30 (p < 0.01), day 60 (p < 0.05), and day 90 (p < 0.001), and similarly healed faster than the placebo-treated ulcers at days 30 and 90 (p < 0.01), but not at day 60. The beneficial effect of phototherapy was more pronounced when the confounding effect of small-sized ulcers was removed from the analysis. Medium- and large-sized ulcers healed significantly faster with treatment (>/=40% rate of healing per month) than placebo or control ulcers (p < 0.05). Conclusion: Phototherapy promotes healing of chronic venous ulcers, particularly large recalcitrant ulcers that do not respond to conventional treatment.

Al-Watban FA.

Photomed Laser Surg. 2009 Feb 4.

Laser Therapy Converts Diabetic Wound Healing to Normal Healing.

Abstract Objective: We have determined optimal laser dosimetric parameters in comparison with polychromatic light-emitting diodes (LEDs) that can speed up healing in four animal models: non-diabetic oval full-thickness wounds, diabetic oval full-thickness wounds, non-diabetic burns, and diabetic burns in Sprague-Dawley rats. Materials and Methods: This series of studies used 532-, 633-, 810-, 980-, and 10,600-nm lasers (visible to far infrared) and polychromatic LED clusters (510-872 nm, visible to infrared) as photon sources. Sprague-Dawley rats (n = 893) were used; however, animals that died before and during the experiments from anesthesia accidents and for any other reason were excluded from statistical analysis. Results: The improvements seen (>10% improvement of impairment) show that phototherapy with the 633-nm laser is quite promising for alleviating diabetic wound and burn healing, and exhibited the best results with 38.5% and 53.4% improvements, respectively. Conclusion: In this induced-diabetes model, wound and burn healing were improved by 40.3% and 45%, respectively, in 633-nm laser dosimetry experiments, and diabetic wound and burn healing was accelerated by phototherapy. This indicates that the healing rate was normalized in the phototherapy-treated diabetic rats. In view of these interesting findings, 633-nm laser therapy given three times per week at 4.71 J/cm(2) per dose for diabetic burns, and three times per week at 2.35 J/cm(2) per dose for diabetic wound healing are recommended as actual doses for human clinical trials, especially after major surgery in those with impaired healing, such as diabetics and the elderly.

Sutterfield R.

Light therapy and advanced wound care for a neuropathic plantar ulcer on a Charcot foot.

J Wound Ostomy Continence Nurs. 2008 Jan-Feb;35(1):113-5; discussion 116-7.

Light therapy is a relatively novel modality in wound care. I used a light-emitting diode (LED) and superluminous diode (SLD) to deliver low-intensity laser light as an adjunctive treatment to a patient with a chronic diabetic foot ulcer. Standard treatment of conservative sharp debridement, off-loading, bioburden management, and advanced dressings was delivered in a WOC clinic setting. This combination of therapies resulted in closure of the neuropathic plantar ulcer within 8 weeks.

Corazza AV, Jorge J, Kurachi C, Bagnato VS.

Photobiomodulation on the angiogenesis of skin wounds in rats using different light sources.

Photomed Laser Surg. 2007 Apr;25(2):102-6.

OBJECTIVE: The aim of this study was to compare the angiogenic effects of laser and light-emitting diode (LED) illumination on wounds induced in rats, with varied fluence. BACKGROUND DATA: The LED is an alternative light source that accelerates wound healing, and its efficiency concerning the angiogenic effect was compared to low-level laser therapy (LLLT). METHODS: The experimental model consisted of a circular wound inflicted on the quadriceps of 120 rats, using a 15-mm-diameter "punch." Animals were divided randomly into five groups: two groups of laser, with dosages of 5 and 20 J/cm(2), respectively, two groups of LED, also with dosages of 5 and 20 J/cm(2), and a control group. Six hours after wound infliction, the treated groups received the diverse applications accordingly and were irradiated every 24 h. Angiogenesis was studied through histomorphometry on days 3, 7, 14, and 21 after the wounds were inflicted. RESULTS: On days 3, 7, and 14, the proliferation of blood vessels in all irradiated groups was superior in comparison to those of the control group (p < 0.05). Treatment with fluence of 5 J/cm(2) was better than the laser group with 20 J/cm(2) on day 21. CONCLUSION: Red LLLT and LED demonstrated expressive results in angiogenesis. Light coherence was shown not to be essential to angiogenesis. However, further studies are needed in order to investigate the photobiomodulatory effects of LED in relation to LLLT in various biological tissues.

Al-Watban FA, Andres BL.

Polychromatic LED in oval full-thickness wound healing in non-diabetic and diabetic rats.

Photomed Laser Surg. 2006 Feb;24(1):10-6.

OBJECTIVE: Our goal was to determine the efficacy of polychromatic light-emitting diode (LED) in the enhancement of wound healing in non-diabetic and diabetic rats. BACKGROUND DATA: LEDs are increasingly used as an alternative light source for phototherapy. METHODS: A cluster of 25 LED photons at 510-543, 594-599, 626-639, 640-670, and 842-872 nm wavelengths with 272-mW output power was used. Male Sprague-Dawley rats (n = 61) were randomly assigned into non-diabetic and diabetic groups and into light treatment groups, that is, control, 5, 10, 20, and 30 J/cm(2). Streptozotocin was used for diabetes induction. Wounds were created using a scalpel after 1 week of wounding. Wounds were measured daily and plotted in time, and the trendline was fitted to obtain slope values. Relative wound healing percentage was computed as follows: RWH% = [(Slope treated - Slope control)/(Slope control)] x 100. The t-test (alpha = 0.05) was used for analysis. RESULTS: The RWH% in the non-diabetic rats was insignificant (p > 0.05) at 5, 10, 20, and 30 J/cm(2) treatments, giving 4.3 +/- 1.97%, 5.4 +/- 1.94%, 4.5 +/- 1.96%, and 1.2 +/- 2.03%, respectively. The healing of diabetic rats was significantly impaired by -11.7 +/- 3.25% (p = 0.02), which was mitigated by 5 J/cm(2) treatment (2.4 +/- 3.02%, (p) = 0.40) and 10 J/cm(2) treatment (-5.5 +/- 3.28%, p = 0.11). Diabetic wound healing using 20 J/cm(2) (-8.7 +/- 3.39%, p = 0.03) and 30 J/cm(2) (-10.90 +/- 1.97%, p = 0.01) affected significant inhibition. CONCLUSION: The effect of polychromatic LED therapy in oval full-thickness wound-healing in the diabetic model with the use of 5 and 10 J/cm(2) is promising. Further studies to determine optimum dosimetry and efficacy of LEDs are recommended.

PMID: 16503782

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